An investigation of the metabolism of N-nitrosodimethylamine and N-nitrosomethylaniline by horseradish peroxidase in vitro.
The demethylation of carcinogenic N-nitrosodimethylamine (NDMA) and N-nitrosomethylaniline (NMA) is catalyzed by horseradish peroxidase in the presence of hydrogen peroxide. NMA is a better substrate for peroxidase than NDMA. The Km values are 0.74 and 3.12 mmol/l for NMA and NDMA, respectively. The oxidation of NDMA and NMA is inhibited by radical trapping agents (nitrosobenzene, glutathione, ascorbate, NADH). This indicates the radical mechanism for the peroxidase-mediated oxidation of both N-nitrosamines. The in vitro metabolism of NMA using peroxidase was investigated in detail. Beside formaldehyde, the metabolites formed from NMA by peroxidase include aniline, p-aminophenol and phenol. Phenol formation presumably arose from N-demethylation of NMA via a benzenediazonium ion (BDI) intermediate while aniline and p-aminophenol from denitrosation of this carcinogen. The results are discussed from the point of view of the role of peroxidases in the metabolism of N-nitrosamines.
Stiborová
M
M
Department of Biochemistry, Faculty of Natural Sciences, Charles University, Prague, Czech Republic. hudecek@prfdec.natur.cuni.cz
Hansíková
H
H
Schmeiser
H H
HH
Frei
E
E
D004128:Dimethylnitrosamine / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D009602:Nitrosamines / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects
D009602:Nitrosamines; C014102:N-methyl-N-nitrosoaniline; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D004128:Dimethylnitrosamine